Serotonin plays a role in several psychiatric disorders, including anxiety, Alzheimer's disease, depression, nausea and vomiting, eating disorders, and migraine. (See Rasmussen et al., "Chapter 1. Recent Progress in Serotonin (5HT).sub.1A Receptor Modulators", in Annual Reports in Medicinal Chemistry, Section I, 30, pp. 1-9, 1995, Academic Press, Inc.; Antigas et al., Trends Neurosci., 19 (9), 1996, pp. 378-383; and Wolf et al., Drug Development Research, 40, 1997, pp. 17-34.) Serotonin also plays a role in both the positive and negative symptoms of schizophrenia. (See Sharma et al., Psychiatric Annals., 26 (2), February, 1996, pp. 88-92.) Serotonin 1A receptor agonists have been shown to increase prefrontal cortex dopamine (DA) release. See Wedzony et al., Eur. J. Pharmacol., 305: 73-78 (1996). Buspirone, a 5HT.sub.1A receptor agonist, has been shown to be efficacious in treating a variety of symptoms associated with ADHD. Serotonin 1A receptor agonists have also been shown to reverse neuroleptic induced dystonia in nonhuman primates, a condition that mimics symptoms of human Parkinson's disease. See Casey, D. E., Neuropsychopharmacol., 10:370S (1994).
Symptoms associated with ADHD have been shown to be relieved by catecholamine releasing drugs such as inethylphenidate, and by postsynaptic .alpha.2 adrenergic receptor agonists such as clonidine. Also, presynaptic .alpha.2 adrenergic receptor antagonists have been shown to increase norepinephrine (NE) release.
A number of 1-(2-pyrimidinyl)-4-[4-(cyclic-imido)butyl]piperidine derivatives have been disclosed as anxiolytic agents which are generally lacking sedative activity. Among these are buspirone, where the cyclic-imido group is 4,4-tetramethylene-piperidine-2,6-dion-1-yl (Wu et al., U.S. Pat. Nos. 3,717,634 and 3,907,801); Casten et al., U.S. Pat. No. 4,182,763); gepirone, where the group is 4,4-dimethylpiperidine-2,6-dion-1-yl (Temple, Jr., U.S. Pat. No. 4,423,049); and ipsapirone, where the group is 1,1-dioxobenzo[d] isothiazol-3(2H)-on-yl (Dompert et al., German patent publication 3,321,969-A1). See also Ishizumi et al., U.S. Pat. Nos. 4,507,303 and 4,543,55; Freed et al., U.S. Pat. No. 4,562,255; Stack et al., U.S. Pat. No. 4,732,983; New et al., U.S. Pat. No. 4,524,026; and Stack, U.S. Pat. No. 4,788,290.
Compounds of the formula (I) below are disclosed in U.S. Pat. No. 5,122,525 as useful for the treatment of anxiety and depression. The use of such compounds for the treatment of addiction is described in U.S. Pat. No. 5,616,885.